It is proposed to study the metabolism of parathyroid hormone to smaller peptide fragments utilizing a biologically active tritiated derivative of the hormone, H3-acetamidino-parathyroid hormone (PTH). Eight of the ten free amino groups of PTH are labeled by this technique but two groups appear unreactive. Experiments to identify which amino groups are unlabeled are proposed, so that it will be possible to identify which segments of the PTH molecule can be detected in the metabolism studies. Utilizing such chemically fully characterized H3-PTH, metabolism of the hormone will be studied in vivo and in vitro. The major metabolites in receptor tissue (kidney-bone) as well as other tissues and in serum will be characterized and their kinetics of appearance and disappearance determined. Utilizing a combination of surgical and perfusion techniques the tissue origin of the major metabolites will be determined. In vitro metabolism of PTH by receptor membranes will be characterized. The products of this process will be determined by a combination of electrophoresis and chromatography techniques. The enzyme responsible for PTH metabolism will be characterized and its relationship to the hormone receptor investigated. Control of PTH metabolism in vitro will be investigated. Potential biological activity of major metabolites of PTH will be investigated. Such potential activities are: regulation of adenylate cyclase, regulation of vitamin D metabolism, regulation of PTH secretion and feed-back regulation of PTH metabolism itself.